A randomized study comparing outcomes of intravesical Gemcitabine, Mitomycin C (as hyperthermic intravesical chemotherapy-HIVEC) and Bacillus-Calmette Guerin in intermediate and high-risk non-muscle invasive bladder cancer.

Abstract

Introduction: Intravesical therapy following transurethral resection of bladder tumor (TURBT) remains the standard of care for non-muscle invasive bladder cancer (NMIBC). However, the global shortage of Bacillus Calmette-Guérin (BCG) and its notable side effect profile have driven interest in alternative agents such as gemcitabine and hyperthermic intravesical chemotherapy (HIVEC), both of which have shown promising results.

Materials and methods: A total of 100 consenting patients with intermediate- and high-risk NMIBC, as per EAU 2020 risk stratification, were enrolled at a single institution between January 2021 and July 2022. Patients were electronically randomized in a 2:1:1 ratio into three groups: gemcitabine (n = 50), HIVEC (n = 25), and BCG (n = 25). Follow-up included cystoscopy and urine cytology every 3 months. Adverse events were assessed and graded using the Modified Clavien-Dindo Classification System.

Results: At 12 months, recurrence-free survival (RFS) was 94% in the gemcitabine group, 84% in the HIVEC group, and 92% in the BCG group (p = 0.675, intention-to-treat analysis). No cases of grade or stage progression were observed. Most recurrences (88.9%) occurred in the high-risk subgroup. Treatment-related side effects were significantly more frequent in the BCG group, while gemcitabine was the most well-tolerated during both induction and maintenance phases. The most common adverse events included lower urinary tract symptoms (LUTS), dysuria, and urinary tract infections (UTIs).

Conclusion: Preliminary findings indicate that intravesical gemcitabine is non-inferior to BCG and HIVEC in terms of short-term efficacy, with a significantly better safety and tolerability profile. These results position gemcitabine as a viable alternative in the management of NMIBC. However, the study's limited sample size and short follow-up period necessitate larger, long-term studies to validate these outcomes.